TY - JOUR
T1 - Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family
AU - Li, Yonghong
AU - Nowotny, Petra
AU - Holmans, Peter
AU - Smemo, Scott
AU - Kauwe, John S.K.
AU - Hinrichs, Anthony L.
AU - Tacey, Kristina
AU - Doil, Lisa
AU - Van Luchene, Ryan
AU - Garcia, Veronica
AU - Rowland, Charles
AU - Schrodi, Steve
AU - Leong, Diane
AU - Gogic, Goran
AU - Chan, Joanne
AU - Cravchik, Anibal
AU - Ross, David
AU - Lau, Kit
AU - Kwok, Shirley
AU - Chang, Sheng Yung
AU - Catanese, Joe
AU - Sninsky, John
AU - White, Thomas J.
AU - Hardy, John
AU - Powell, John
AU - Lovestone, Simon
AU - Morris, John C.
AU - Thal, Leon
AU - Owen, Michael
AU - Williams, Julie
AU - Goate, Alison
AU - Grupe, Andrew
PY - 2004/11/2
Y1 - 2004/11/2
N2 - Although several genes have been implicated in the development of the early-onset autosomal dominant form of AlzheimeKs disease (AD), the genetics of late-onset AD (LOAD) is complex. Loci on several chromosomes have been linked to the disease, but so far only the apolipoprotein E gene has been consistently shown to be a risk factor. We have performed a large-scale single-nucleotide polymorphism (SNP)-based association study, across the region of linkage on chromosome 12, in multiple case-control series totaling 1,089 LOAD patients and 1,196 control subjects and report association with SNPs in the glyceraldehyde-3-phosphate dehydrogenase (G-APD) gene. Subsequent analysis of G-APD paralogs on other chromosomes demonstrated association with two other paralogs. A significant association between LOAD and a compound genotype of the three GAPD genes was observed in all three sample sets. Individually, these SNPs make differential contributions to disease risk in each of the case-control series, suggesting that variants in functionally similar genes may account for series-to-series heterogeneity of disease risk. Our observations raise the possibility that GAPD genes are AD risk factors, a hypothesis that is consistent with the role of GAPD in neuronal apoptosis.
AB - Although several genes have been implicated in the development of the early-onset autosomal dominant form of AlzheimeKs disease (AD), the genetics of late-onset AD (LOAD) is complex. Loci on several chromosomes have been linked to the disease, but so far only the apolipoprotein E gene has been consistently shown to be a risk factor. We have performed a large-scale single-nucleotide polymorphism (SNP)-based association study, across the region of linkage on chromosome 12, in multiple case-control series totaling 1,089 LOAD patients and 1,196 control subjects and report association with SNPs in the glyceraldehyde-3-phosphate dehydrogenase (G-APD) gene. Subsequent analysis of G-APD paralogs on other chromosomes demonstrated association with two other paralogs. A significant association between LOAD and a compound genotype of the three GAPD genes was observed in all three sample sets. Individually, these SNPs make differential contributions to disease risk in each of the case-control series, suggesting that variants in functionally similar genes may account for series-to-series heterogeneity of disease risk. Our observations raise the possibility that GAPD genes are AD risk factors, a hypothesis that is consistent with the role of GAPD in neuronal apoptosis.
UR - http://www.scopus.com/inward/record.url?scp=8144228132&partnerID=8YFLogxK
U2 - 10.1073/pnas.0403535101
DO - 10.1073/pnas.0403535101
M3 - Article
C2 - 15507493
AN - SCOPUS:8144228132
SN - 0027-8424
VL - 101
SP - 15688
EP - 15693
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 44
ER -